Researchers from Italy developed inhalable calcium phosphate nanoparticles (CaP-NPs) that showed potential to counteract Pseudomonas aeruginosa infection, the most prevalent airway pathogen in patients with cystic fibrosis (CF), as published in the Journal of Inorganic Biochemistry.

“CaP-NPs can be functionalized with antimicrobial Col [colistin] with a payload up to about 50 mg of Col per g of CaP-NPs, thanks to the establishment of electrostatic interaction between the positively charged amine groups of Col and the negatively charged surface of CaP-NPs,” the researchers explained.

They observed a significant reduction in colony formation after treating P aeruginosa biofilm with either colistin or colistin-loaded CaP-NPs when compared to untreated biofilm or biofilm treated with CaP-NPs only. Hence, antimicrobial and antibiofilm effects of colistin were maintained after its incorporation into CaP-NPs.

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The colistin-loaded CaP-NPs did not interact with mucin, the main component of airways mucus, and were able to cross a layer of artificial mucus. These findings suggested that colistin could be efficiently delivered into the infection site, where it would disrupt bacterial cell organization.

“Inhaled antibiotics present poor capability of penetrating the sticky mucus to target the enclosed bacteria and to reach peripheral airways by overcoming mucosal plugs at the central bronchi and bronchioles,” they explained. Therefore, to counteract its poor lung bioavailability, patients are administered high doses of the drug.

The use of colistin-loaded CaP-NPs would enable the use of a lower concentration of colistin, thereby minimizing its toxicity. In vitro assays showed that except for high doses (>125 μg mL-1), the acute administration of CaP-NPs was not cytotoxic for pulmonary cells. The microbiological experiments performed in this study used a P aeruginosa strain isolated from a patient with CF.

Reference

Iafisco M, Carella F, Degli Esposti L, et al. Biocompatible antimicrobial colistin loaded calcium phosphate nanoparticles for the counteraction of biofilm formation in cystic fibrosis related infections. J Inorg Biochem. 2022;230:111751. doi:10.1016/j.jinorgbio.2022.111751